Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates.Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65–74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale.Among victims ≥15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC ≥ 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims’ bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol.Psychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms—for instance drug-induced long-QT syndrome—by which drugs may contribute to drowning.The online version of this article (doi:10.1186/s12889-017-4306-8) contains supplementary material, which is available to authorized users. Drowning is one of the world’s leading causes of unintentional deaths . Many stOn the other hand, only limited information is available as to the role of drugs other than alcohol in unintentional drowning. The effects of many psychotropic drugs on cognition and judgment are, however, similar to those of alcohol . Their iFinland (population 5.2 million) has one of the highest mortality rates by drowning among all high-income countries , 17, 18.This nationwide study is based on a dataset of 2828 consecutive fatal drownings occurring in Finland during a 10-year period (2000–2009) for which post-mortem (PM) toxicology was performed; unlike a similar study in Sweden,  independWe conducted a descriptive and retrospective study, based on individual-level data, for all drownings and their association with drugs and alcohol among Finnish residents of all ages who had undergone a medico-legal autopsy and PM toxicology, from 2000 through 2009, the last year for which detailed attribution of impairment by drug level was available.Toxicological data concerning all fatal drowning cases (ICD-10 “nature of injury” code: T75.1) came from the database of the Laboratory of Forensic Toxicology, Department of Forensic Medicine, University of Helsinki. During the study period, this laboratory carried out—by statute and on request of the medical examiner performing the medico-legal autopsy-PM alcohol analyses and all other toxicology tests for the entire country. In most cases, whenever available, peripheral blood samples were from the femoral vein, and if not available, from other sites. Routine toxicological samples obtained at autopsy also include urine and vitreous humor. Blood ethanol concentration was determined by a dual-column head-space gas-chromatographic method. The final result is the average of the four independent measurements. Depending on the category of the substance in question, common and abused drugs were screened from a urine or blood sample by a relevant method. The quantitative results used in this study were always based on a blood sample. All relevant analytical methods in the laboratory (Testing Laboratory No. T115) have been accredited since 1997 by the Centre for Metrology and Accreditation according to SFS-EN 45001 ISO/IEC Guide 25. Drugs were classified according to the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) codes , 22. Then = 546), homicide by drowning , and drowning of undetermined intent , as well as accidental drownings with an external cause-of-injury code other than drowning (n = 318), e.g. land-traffic accidents and exposure to force of nature leading to drowning [The original data set included 2828 fatal drownings. Excluded from the data were suicidal drowning  drugs (ATC: N01-N06) were considered, with the exclusion of caffeine (N06BC01) and nicotine (N07BA01). We explicitly acknowledge that drugs often have effects on organ systems other than those implied by the ATC classification. Drowning deaths with BAC values ≥50 mg/dl were considered as alcohol-related.The degree of psychomotor impairment resulting from various psychotropic drug concentrations was evaluated by means of a 6-grade scoring system from 0 (no effects) to 6 (probable effects) based on the expected level of impairment for each level of drug reported  examined during the study period at this laboratory. Of these unintentional drownings, 100% were tested for alcohol and 91.5% for other drugs Table . The difFor all the 1746 unintentional drownings at any age, 1059 (60.7%) tested positive for alcohol and 458 (26.2%) for at least one psychotropic drug. Only the 1697 unintentional drowning victims aged 15 years or older were further considered in this study.Table Boating-related drowning showed the highest percentage to be alcohol-positive (BAC ≥ 50 mg/dL) victims (65.0%). Conversely, psychotropic drugs were more prevalent in victims of non-boating drowning. Almost one-third of these victims had psychotropic drugs in their blood alone or in association with alcohol (BAC ≥ 50 mg/dL). Six cases were psychotropic-drug-positive and had a BAC between 0 and 50 mg/dL, of which one was boating-related and five non-boating-related Table .Table 4UThe male-to-female rate ratio in alcohol-positive non-boating drowning was 6:1, and in boating-related drowning, the corresponding value was as high as 27:1. Percentages of alcohol-positive cases were, however, similar in both genders.In psychotropic-drug-positive cases, gender distribution was more even; being approximately 4:1 in non-boating- and 11:1 in boating-related drowning Table . AlthougAlthough no evident age-group peaks occurred for both alcohol- and drug-positive cases, the highest percentage of positive cases for both alcohol- and drug-positive victims was in those 20 to 54 years old. In those over 54, a progressive decrease occurred in the percentage of alcohol-positive victims and, conversely, a fairly stable percentage or even an increase in drug-positive cases among the elderly Fig. .Fig. 1UnIn alcohol-positive victims, the most frequently measured BAC ranged from 200 to 249 mg/dL . BAC ranges between 250 to 299 and 150 to 199 mg/dL represented the second and third largest groups, with 234 (21.2%) and 221 (20.0%) victims. BAC was ≥300 mg/dL in 118 victims (10.7%) and below 100 mg/dL in 101 (9.2%)  Table .Based on the grading score for psychotropic-drug-positive unintentional drownings in our 453 victims, we distinguished a group 0 (no effects of drugs), as well as drug-affected groups 1 to 3, and 4 to 6 .Among our victims of unintentional drowning, 14.6% tested positive for psychotropic drugs with a grade of 4 to 6 Table . Such hiHigh drug concentrations (grade 4–6) that may well have contributed to drowning were found in 3.5% (59/1697) of overall unintentional drowning victims who showed no alcohol. Most of these cases were non-boating drownings Table .Table 8UAmong the 247 unintentional drowning victims graded 4 to 6 for psychotropic drugs, as many as 59 (23.9%) had no alcohol in their blood.In 6.1% of the cases graded 4 to 6 for psychotropic drugs (15/247), BAC was positive but <100 mg/dL. The highest association between high psychotropic drug concentration (grade 4–6) and alcohol was in victims having BAC ≥ 100 mg/dL, with a peak for BAC 200 to 249 mg/dL Fig. .Fig. 3UnAccording to WHO standard mortality data and a previous nation-wide survey on drowning,  the uninThe 255 drowning cases for which no toxicological analysis was performed most likely represent a heterogeneous group. This group includes drowning cases for which the medical examiner considered, based for instance on the victim’s age and circumstances, that a role for alcohol and drugs was unlikely. Among the non-tested victims, 123 were under the age of 15 or over 65. Victims dying in hospital may have been under the influence of alcohol and/or drugs during the submersion events. PM toxicology is, however, not usually performed in cases with a prolonged interval between submersion and death in hospital.Whereas studies on unintentional drowning and alcohol have been performed in high-income countries, only very limited data are available on unintentional drowning and psychotropic drugs, , 25 and An association between alcohol and unintentional drowning has been highlighted in many studies , 8, 27. SF does not supply BAC values, however, making evaluation of the causal effects of alcohol on drowning impossible. From the present data, a concentration-effect relationship between alcohol and drowning is apparent. High levels of alcohol thus almost certainly contribute to drowning, while boating, swimming, or engaging in any other activities in aquatic settings. In addition to dose-dependent psychomotor impairment and lowering of the cognitive processes, alcohol may promote risk-taking behaviour. This will likely lead to underestimating and misinterpreting the risks of swimming or boating under challenging circumstances or to neglect of safety regulations: for example, using a life-jacket or –vest .Considering cases with BAC over 50 mg/dL to be alcohol-related reduces the possible bias of PM alcohol production . Future On the other hand, our data set revealed that as much as 10.7% of the cases had a BAC ≥ 300 mg/dL, a value considered potentially lethal , 37. AltThe correlation of alcohol and drowning emerges in several studies, but the effect of drugs’ contribution to drowning has not been extensively studied. Among the few studies is one in Sweden, during an 18-year study period, in which, of 2075 unintentional- drowning victims, 462 (22%) were positive for psychotropic drugs . In bothHere, we focused on psychotropic drugs and their potential involvement in unintentional drowning . ConcentLimitations exist in the grading system and evaluation method we used. Similar grading systems appear in studies conducted in the field of traffic medicine and psychotropic drugs,  but the PM toxicological studies differ from toxicology performed on a living individual, such as in the context of drunken driving or driving under the influence of drugs. In this regard, a relevant aspect is the PM drug redistribution that may challenge the interpretation of PM drug concentration , 46. A bInterestingly, our level of psychotropic drugs present in one-third of unintentional drowning victims, was a value similar to that reported in Sweden . PsychotOur findings suggest that psychotropic drugs may play a significant role in drowning, as they did in up to 14.6% of our cases, independently or in association with alcohol. Among our overall unintentional drowning victims, 3.5% were alcohol-negative but had high blood concentrations of one or more psychotropic drugs, making the contribution of psychotropic drugs to such drowning cases possible, even very probable. In four additional cases (0.24%) in which drug concentrations were high and BAC levels were between 10 and 49 mg/dL, the role of psychotropic drugs may well have enhanced the effects of alcohol in the events leading to drowning.In the remaining 10.8% of our unintentional drowning victims, these had a BAC ≥ 50 mg/dL and a high blood concentration of one or more psychotropic drugs. In these cases, the drugs’ contribution to drowning may also have been possible or even very likely. It is challenging, however, to disentangle the effects of alcohol from those of psychotropic drugs in the events leading to drowning. Psychotropic drugs have known additive effects on the adverse effects of alcohol, , 49 makiOur findings may have important implications for prevention, when considering the prescribing and use of psychoactive drugs in patients who are keen to engage in swimming and other aquatic activities; especially those likely to use alcohol.Of our over 70 different psychotropic drugs found, the most common were desmethyldiazepam, diazepam, oxazepam, and temazepam, all of which are benzodiazepines. Impaired cognitive and psychomotor skills are well-known side-effects of benzodiazepines, , 50 effeWhereas psychomotor impairment associated with benzodiazepines can be sufficient to elevate the risk of drowning, among the 10 most common psychoactive and non-psychoactive drugs detected in drowning victims are several known to cause drug-induced long-QT syndrome (DILQTS); this may lead to severe arrhythmias –56. Two Genetically determined long-QT syndromes are associated with sudden cardiac death and drowning, , 61 implFurther steps in investigating the actual role and mechanism of drugs in unintentional drowning will require appropriate consideration of pre-drowning activity, settings, and events leading to death in water. Finally, we will need specific evaluation of whether toxicological findings in victims of unintentional drowning differ from those of the entire population and the subset of the population engaged in water-related activities, as well as the victims of unintentional injury deaths in general, and those of intentional drowning.Psychotropic drugs other than alcohol may be, alone or in association with alcohol, an overlooked factor contributing to fatal unintentional drowning in almost 15% of cases. The impact of psychoactive drugs on drowning may be aggravated by the additive effects of alcohol in aquatic settings. The actual mechanism by which psychoactive drugs or alcohol or both combined may contribute to drowning deserves further investigations; the mechanism may have crucial implications for drug prescription and dispensing practices. In addition to impairing cognitive and psychomotor performance in aquatic settings, other mechanisms, such as drug-induced fatal arrhythmias, may contribute to some otherwise unexplained deaths in water.Additional file 1:Overall drugs found in unintentional drowning, 2000–2009. (DOCX 13 kb)Additional file 2:Nervous system drugs in unintentional drowning by ATC group and subgroups, 2000–2009. (DOCX 13 kb)Additional file 3:Fatal unintentional drowning in Finland 2000–2009 by age and gender, according to Statistics Finland and the Laboratory of Forensic Toxicology, University of Helsinki. (DOCX 15 kb)


Patient characteristics and clinical details were extracted from medical records. Regression was defined as all coronary arteries having a z-score of ≤3. A major adverse event was defined as cardiac death, myocardial infarction, cardiogenic shock, or any coronary intervention. Regression-free and event-free rates were calculated using the Kaplan–Meier method. We included 52 patients with giant CAA of which 45 had been monitored since the acute phase. The 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65, respectively. The 5-year, 10-year, and 15-year event-free rates were 0.79, 0.75, and 0.65, respectively. Four children, whose CAA would not have been classified as ‘giant’ based on absolute diameters instead of z-scores, had experienced an event during follow-up. Conclusion: We found a high percentage of children in whom the lumen of giant CAA completely normalized. Four children not classified as ‘giant’ based on absolute diameters with z-scores of ≥10 experienced a cardiac event. Hence, the use of z-scores seems to be justified.Kawasaki disease (KD) is a pediatric vasculitis. Its main complication is the development of coronary artery aneurysms (CAA), with giant CAA at the end of the spectrum. We evaluated regression and event-free rates in a non-Asian cohort of patients with giant CAA using the current z-scores adjusted for body surface area instead of absolute diameters. KD patients with giant CAA (The online version of this article (doi:10.1007/s00246-017-1590-0) contains supplementary material, which is available to authorized users. Kawasaki disease (KD) is a pediatric vasculitis of the medium-sized arteries . Althougz-scores. Z-scores are preferred as they correct the absolute size in mm for body surface area (BSA) of the child [At the extreme end of the spectrum of CAA are giant CAA. In Asian cohorts, giant CAA typically do not regress, but evidence is scarce in the current era of more standardized treatment protocols. Most studies use cut-offs based on absolute diameters instead of he child .Persistence of giant CAA causes an increased chance of thrombosis within and perfusion abnormalities distal to the CAA, potentially inducing ischemia and myocardial infarction (MI) . Also, tIn this study, we report on a cohort of patients with giant CAA based on z-scores, evaluating regression and cardiac complications.The Academic Medical Centre in Amsterdam (The Netherlands) is a tertiary referral center for patients with KD. At our center, we have a multidisciplinary outpatient clinic for cardiologic and/or (immunologic) long-term follow-up. The cohort of KD patients at out center consists of patients who were admitted to our center during the acute phase and who are admitted to other hospitals during the acute phase and are referred to our center for follow-up.Patients with KD visiting our outpatient clinic between January 1999 and September 2015 were eligible. Patients were included if they had giant CAA during the acute phase of the disease. For analyses purposes, patients who were missed during the acute phase and patients of whom no information of the acute phase was available were excluded.We retrospectively extracted clinical details from the medical records, i.e., gender, age at disease onset, (in)complete disease presentation, treatment with IVIG including the day of first IVIG treatment, IVIG re-treatment, treatment with steroids, aspirin and/or anticoagulation therapy, and size of the CAA at initial presentation and during follow-up.z-score of the left main coronary artery, right coronary artery, or left anterior descending artery within the first 6 weeks was chosen in order to specify CAA [The CAA status was taken from information in echocardiography reports. The highest cify CAA , 6. Giancify CAA . When uscify CAA .z-score of 3 to 3.5 was present.During follow-up, z-scores based on echocardiography, coronary angiographies (CAG’s), Magnetic Resonance Imaging (MRI’s), or Computer Tomography (CT)-scans were calculated. Regression was defined as all coronary arteries having a z-score of ≤3. CAA were also considered to have regressed when only a dilation of the origin of the coronary arteries with a A major adverse event was defined as cardiac death, MI, cardiac arrest or cardiogenic shock, coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI).We calculated the number of days until all coronary arteries were regressed as demonstrated by an imaging procedure. If regression did not occur, the follow-up time was calculated until the date of the last imaging procedure with a maximum of 15 years. A regression-free survival curve was then constructed by means of the Kaplan–Meier method.If imaging suggested ischemia or infarction without preceding clinical presentation, the time from diagnosis until the date of the imaging was calculated. Patients were censored if no event occurred; follow-up time was calculated until the last registered imaging procedure with a maximum of 15 years. We assessed the 5-, 10-, and 15-year event-free survival using Kaplan–Meier analysis.In total, 52 patients with giant CAA visited our outpatient clinic. In six patients, KD was missed. These six patients  presented with cardiac complaints due to ischemia and/or MI based on thrombus formation in a CAA or stenosis proximal or distal to a CAA. None of the patients had signs of atherosclerosis or cardiac disease, making KD the most likely cause of their giant CAA. In one extra patient, no information about the acute phase of the disease was available.The remaining 45 KD patients had echocardiographic examinations within 6 weeks after acute disease onset. Patient characteristics and clinical data are shown in Table In 13 (29%) children, aspirin was discontinued after the CAA were considered to have regressed completely. They had received aspirin for a median of 17.3 months . None of these children experienced a cardiac event during or after discontinuation of aspirin therapy.The 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65, respectively  children were girls, of which 2 had completely regressed CAA. A total of 23 (50%) children were under the age of 1 during the acute disease, of which 4 regressed within the first and an additional 2 within the second year. Of the 22 children over the age of 1 during the acute disease, 2 regressed within a year and 1 other child within the first 2 years.Of the 19 children receiving a second IVIG dose, 6 had completely regressed CAA in a median time of 2.9 years (IQR 1.3–4.4). Of the 11 children receiving subsequent steroid treatment, 5 had regressed in a median time of 4.0 year (IQR 1.2–4.6).Of the 14 children with an original z-score of 10–15, 11 (80%) went into complete regression. Of the children with an original z-score of 15–20, only 4 (25%) out of 16, and for the children with an original z-score of > 20, we observed that only 3 (20%) out of 15 completely regressed .p = 0.041).A total of 12 cardiac events or interventions took place after a median time of 0.17 years (range 0.02–13.58 years) . In 3 of them, the ischemia was only apparent upon contrast-enhanced imaging of the heart as clinical symptoms and cardiac signs were absent.Five children had a cardiac arrest or cardiogenic shock. Four children had undergone CABG at a median age of 15.9 years (range 10.5–22.0 years).Four of the children who experienced MI obtained a cardiac MRI with adenosine stress testing during follow-up, showing hypo- or akinesia of the wall in the infarcted areas but an otherwise good systolic function. Another 15 children obtained a MRI with adenosine stress testing, showing no functional abnormalities.In 8 children, coronary arterial stenosis was apparent with subsequent CABG in 3 and a coronary balloon dilation in 1 patient(s). In 2 children, the stenoses became only apparent at autopsy and in 2 children the stenosis did not require immediate intervention. Most stenoses were seen directly proximal or distal to the CAA. None of these children had completely regressed CAA. Five of the children with arterial stenoses had experienced MI. In Table In a large Dutch cohort of KD patients with giant CAA based on z-scores, visiting our outpatient clinic during a 15-year period, we calculated 1-year, 2-year, and 5-year regression-free rates of 0.86, 0.78, and 0.65. The 5-year, 10-year, and 15-year event-free rates were 0.79, 0.75, and 0.65. This is the first study solely evaluating patients with giant CAA based on z-scores in a Western population.z-scores decreased to <3 more than 5 years after disease onset. The decline of the z-scores in these children is suggested to be due to the normal growth of these children rather than a decline of the absolute CAA diameter. Our finding that regression mainly takes place in the first 5 years is supported by earlier studies. Lin et al. found a 5-year persistence rate of 46% for medium-sized CAA with little regression after [A study by Chih at al., following 27 children with giant CAA ≥ 8 mm), found that none completely regressed  mm, foun. On the on after . Kato eton after .z-scores are helpful in identifying patients at high risk. Also, all but one patient in our cohort received IVIG, improving outcome as IVIG was found to be an independent risk factor for major adverse cardiac events (MACE) in a recent study [In a large Japanese study, Tsuda et al., studying 245 patients with giant CAA ≥8 mm), found 10-, 20-, and 30-year cardiac event-free survival rates of 64, 48, and 36%, respectively [ mm, founMost events happened within the first months after the acute phase. Yet, in 3 patients, echocardiography or MRI showed signs of a small MI or subclinical ischemia, 10 years or more after the acute disease .Although conventional coronary angiography is still the gold standard to assess coronary anatomy and possible stenosis, this technique is invasive and exposes the child to radiation. Low-dose CT angiography is becoming more widely available and decreased the radiation burden significantly . Using eAlthough we only observed cardiac events in children with persisting CAA at that time, it is unlikely that regression of CAA to a normal diameter of the arterial lumen will eliminate all future cardiovascular risk. Even if the lumen has a normal diameter, the arterial wall is supposed to be damaged and unable to adequately dilate upon increased cardiac demand . In a reWe calculated z-scores from absolute diameters described in echocardiography, CAG-, MRI-, or CT-reports. Since approximately half of the patients were admitted to other hospitals during the acute phase of the disease, pediatric cardiologists in other centers had generated many of the early echocardiographies. Echocardiography is known for its measurement uncertainty, which could have influenced the regression as well as the time-to-regression.For the time-to-regression, we registered the time until the first imaging procedure that demonstrated normality of all coronary arteries. The precise time of regression can therefore not exactly be defined. Hence, the time-to-regression has to be considered as the maximum time in which regression took place.As this was a retrospective study, imaging was not performed according to a set protocol. This means subclinical ischemia could have been missed in children if no suitable imaging technique was performed.In a Dutch cohort of KD patients with giant CAA based on z-scores followed up from the acute phase, the 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65. The 5-, 10-, and 15-year major adverse event-free rates were 0.79, 0.75, and 0.65, respectively. In 4 children whose CAA would not have classified as being ‘giant’ according to absolute diameters instead of z-scores, a cardiac event took place. Therefore, z-scores are suggested to be a more sensitive tool to decide on life-long regular follow-up of KD children.Below is the link to the electronic supplementary material.Supplementary material 1 (DOCX 21 KB)


HIGHLIGHTSFe incorporation significantly accelerated the adsorption of CPX on MCM-41.Fe leaching can be ignored when pH was higher than 4.0.pH played an important role in CPX adsorption on Fe-MCM-41.Co-effect of CPX and metal cations on Fe-MCM-41 was investigated.−1 at 120 min of reaction time, which was mainly attributed to surface complexation. The promotion of hydrophobic effect, electrostatic interactions, and π-π electron donor-acceptor interaction also played coordinate roles in the adsorption process. The experimental kinetic data followed both the pseudo-second-order and intra-particle diffusion models, while the adsorption isotherm data fit well to Freundlich model at high temperature. Thermodynamic study showed that the adsorption was spontaneous. Under the effect of electrostatic interaction, pH of the solution strongly affected CPX adsorption. Five representative metal cations  were chosen to study the effects on CPX adsorption and their complexation. The inhibiting effect of metal cations on CPX adsorption was sequenced in the order of Cu > Ni > Pb > Cd > Ca, which followed the same order as the complexation stability constants between CPX and cations. The Fe-MCM-41 adsorbent possessed excellent reusability for 4 cycles use, suggesting a potential applicability of Fe-MCM-41 to remove CPX in water.Fe-MCM-41s with various molar ratios of silicon to iron  were prepared to investigate adsorption properties of ciprofloxacin hydrochloride (CPX) in aqueous solutions. Fe-MCM-41s were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption/desorption isotherms, and infrared spectroscopy (FT-IR). Effects of silicon-iron ratio, adsorbent dosage, pH, and temperature were conducted to explore the adsorption mechanism of CPX on Fe-MCM-41. The results showed that the introduction of iron facilitated the absorption quantity for CPX from 20.04 to 83.33 mg g During the last decades, pharmaceuticals and personal care products (PPCPs) among the emerging contaminants have caused more concern of environmental research than the conventional priority pollutants Arp, . With abAs a member of the M41S family, MCM-41 applied to adsorption area has attracted more awareness because of its hexagonal arrays of uniform channels, high surface area and pore volume and hydrothermal stability  and ferric nitrate (Fe(NO3)3·9H2O) were obtained from Sinopharm Chemical Reagent Co. Ltd. . For the adsorption experiments, ciprofloxacin hydrochloride (CPX) was obtained from Macklin Biochemical Co. Ltd. . Acetonitrile was chromatography grade and was purchased from Tianjin Kemiou Chemical Reagent Co. Ltd. . All the other metals were nitrate salt species and analytical grades. Deionized water was used throughout the study. pH value of the solution was adjusted with 0.1 M hydrochloric acid (HCl) and sodium hydroxide (NaOH).These reagents were used to synthesize and modify MCM-41: cetyltrimethyl ammonium bromide (CTAB), sodium silicate  was stirred at 313 K for 15 min. H2SO4 (2 M) was added dropwise to form a gel. After adding CTAB (7.28 g dissolved in 25 ml water at 338 K) to the gel, the mixed solution was stirring for 30 min, and then aged at 418 K for 48 h. The product gotten was filtered after natural cooling, washed with deionized water and dried. Finally, the sample was calcined for 6 h at 823 K to obtain MCM-41. Fe-MCM-41 was prepared from the same route besides adding Fe(NO3)3·9H2O as iron modification to the solution before pH adjustment. The samples were designated as Fe-MCM-41(x) , where x was denoted as different molar ratios of Si to Fe for as-synthesized materials.MCM-41 was prepared via a hydrothermal treatment using Na2 adsorption/desorption isotherms  was used to calculate the surface area. The pHpzc value was measured by potentiometric titration. The leaching iron content of the solution was determined by atomic absorption Spectrophotometer . The FT-IR absorption spectra  was obtained over the range 4,000–400 cm−1.The low-angle XRD measurements  were carried out in the 2θ ranges of 1.0–8.0°. The N−1.The concentration of CPX was quantified using HPLC  consisting of a UV detector (SPD-10AV) at 278 nm and a Diamonsil C18 column . The mobile phase used for detection of CPX was acetonitrile/0.01 M potassium dihydrogen phosphate  and the flow rate was 1.0 mL min−1, initial pH = 5.40) in flasks and the mixture stirred at 303 K up to beyond the equilibrium time. The rotating speed was set to 175 rpm. Additional experiments were also performed to study the effects of equilibrium time, dosage, pH, temperature and metal cations on the adsorption properties. To study the impact of various metal cations on the adsorption behavior of CPX, predetermined amounts of Ca(II), Cu(II), Ni(II), Pb(II), Cd(II) were introduced to obtain 0.01 M ionic strength solutions at 303 K, respectively. Controls without Fe-MCM-41 were considered to explain losses from adsorption to flasks. All experiments were run in triplicate under the same conditions.For adsorption experiments, 0.04 g of adsorbent was mixed with 200 mL of CPX solution (20 mg L−1) were chosen based on preliminary experiments, which controlled the adsorbed amount of CPX between 30 and 90% of the initial amounts. A study of reusability was carried out by adsorption/desorption for four times.A series of adsorbent doses from 30 to 60 mg were selected to discuss the effect of dosage. The pH effects experiments were conducted by adjusting the pH between 3 and 11. To study the impact of various metal cations on the adsorption behavior of CPX, predetermined amounts of Ca(II), Cu(II), Ni(II), Pb(II), Cd(II) were added to obtain 0.01 M ionic strength solutions at 303 K, respectively. The isotherms were obtained by batch experiments performed at 293 ± 0.5, 303 ± 0.5, 313 ± 0.5 K, respectively. The initial concentrations of CPX  with Fe3+ (0.63 Å) in the structure of material, the extension of radius enlarged the pore sizes and decreased surface area. Moreover, XPS was provided to clarify the chemical phase of Fe species in the synthesized Fe-MCM-41. XPS spectrum in Figure 3/2 and Fe2p1/2, reflecting iron species existed as Fe3+ in Fe-MCM-41  value. Also, based on the second-order model, the calculated qe  was a good agreement with the experimental qe  values, besides qe  increased from 20.12 to 95.24 mg g−1 with Fe content. Compared the various adsorption capacities of CPX with those reported adsorbents such as Graphene oxide/calcium alginate (GO/CA)  was the fraction at time t, Bt denoted a mathematical function of F.Where The linearity of the plot was applied to differentiate the controlled rates of adsorption between external transport and intra-particle diffusion. The plot in Figure i also proved that the adsorption rate became slower during the adsorption process. It concluded that the intraparticle diffusion was present while some other mechanisms might be involved.The second-stage portion became slower than first stage due to the weak adsorption between CPX and the surface atoms of the solid. The third-stage portion tended to ease up and reached final equilibrium. It could be attributed to the smaller pores, lower concentration of CPX and enhanced electrostatic repulsion (between CPX and the adsorbents surface). What's more, comparisons of the values of kThe adsorption isotherm in Figure R2 = 0.9459) at 293 K while Freundlich model yielded the best fit at temperatures 303 K (R2 = 0.9544) and 313 K (R2 = 0.9675). This implied monolayer adsorption with a value of 133.33 mg g−1 obtained for qmax and evenly distribution of the adsorption sites at low temperature. However, as temperature rose, the Freundlich equation became even more accurate to assess the adsorption process. It was possible to deduce that the thermal treatments activated more active sites for adsorption as described above. Molecules of CPX retained two monolayer adsorptions when the pore diameter of Fe-MCM-41 was greater than molecule diameter of CPX, and despite reversible adsorption occurred meanwhile , entropy change (ΔS), and the Gibb's free energy (ΔG), were evaluated to obtain insights into the changes of adsorption processes using the Van't Hoff equation  and (8):As listed in Table G-values were obtained in the range of 293–313 K, revealing the feasible and spontaneous of adsorption process. The positive ΔH-value demonstrated an endothermic process while the positive value of ΔS indicated that the organization of the CPX molecular at the solid- liquid interface became more random than low temperature.The negative Δpzc of Fe-MCM-41(20) was estimated to be around 5.4, the surface charge of Fe-MCM-41(20) remained negative over the range of pH (5.4 < pH < 11.0) in this study. Therefore, the speciation of CPX molecules were regarded as the mainly factor to this pH range (5.4 < pH < 11.0) influence on the adsorption level. Figure a1 and pKa2 values of CPX were 6.1 and 8.7, respectively. Most of CPX molecular were in cationic form with protonated amine group in the piperazine moiety when pH was less than 6.1. Cationic CPX generated electrostatic attraction with negatively charged Fe-MCM-41(20) on the surface, accordingly promoting the adsorption. As displayed in Figure The pH2+, [M(AH)2]2+, [M(AH)A]+. Because of the solution under neutral conditions, [M(AH)]2+ was the main form. Compared to other divalent metals, the complexation ability of CPX with Cu was much stronger, and the result agreed with the heavy metals which exhibited different removal efficiency.Metal cations with relatively high concentration could impact CPX adsorption. The presence of Cu(II) facilitated the adsorption of CPX on montmorillonite at pH > 6.0 (Pei et al., It was important for an adsorbent with good reuse performance in practical application. According to the investigation of pH influence, the adsorption capacity of CPX on Fe-MCM-41 was negligible when the pH was above 10. It indicated that of CPX could desorbed from the absorbent surface using 0.1 M NaOH solution as the desorption agents possibly, then the adsorbent was filtered, washed and dried at 358 K. The regenerated adsorbent was tested by four cycles of adsorption/desorption process under the same conditions. Figure Fe-MCM-41s prepared from a hydrothermal process were used as adsorbents to adsorb the CPX in aqueous solutions. Experimental results described that Fe-MCM-41 with Si/Fe = 20 exhibited the best CPX removal efficiency. The XRD and TEM results confirmed that the hexagonal mesoporous structure maintained after iron doping. A combination of multiple effects including electrostatic interaction, surface complexation, hydrophobic effect and π-π interaction on the adsorption process were confirmed under different reaction conditions. The experimental kinetic data showed that the adsorption was a chemical-controlling and multi-step process, Fe-MCM-41 showed the better adsorption property. Strong acidic/alkaline environment was not conducive to the adsorption process. The adsorption performed a higher adsorption affinity at higher temperature was a spontaneous exothermic process. Moreover, due to the depression of Me-CPX complex, metal cations decreased CPX adsorption on Fe-MCM-41 surface. As the same order as the complexation stability constants of CPX, Cu impacted CPX adsorption most. Fe-MCM-41 exhibited stable performances for 4 cycles use without deterioration which could possibly applied to wastewater treatment including POPs.YW: Conducted all the experiments; YT: Supervised the project; LL: Revised the manuscript; PL and XL: Provided assistance in setting up the gears; WC and YX: Helped analysis the data.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There is currently limited information regarding the prognostic ability of the dNLR-PNI  for hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in patients with intermediate-to-advanced HCC after transarterial chemoembolization (TACE).A total of 761 HCC patients were enrolled in the study. The dNLR-PNI was retrospectively calculated in these patients, as follows: patients with both an elevated dNLR and a decreased PNI, as determined using the cutoffs obtained from receiver operating characteristic curve analysis, were allocated a score of 2, while patients showing one or neither of these alterations were allocated a score of 1 or 0, respectively.P < 0.001).During the follow-up period, 562 patients died. Multivariate analysis suggested that elevated total bilirubin, Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were independently associated with unsatisfactory overall survival. The median survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 , 16.0 (95% CI 12.2–19.7) and 6.0 (95% CI 4.8–7.2) months, respectively (The dNLR-PNI can predict the survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and should be further evaluated as a prognostic marker for who are to undergo TACE treatment. Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths worldwide . HistoriSeveral blood-derived parameters have been demonstrated to be associated with survival of HCC patients. Especially, with the advantage of being readily available from routine tests of blood cell counts and liver function, the derived neutrophil-to-lymphocyte ratio (dNLR) , 5 and pFurthermore, most previous studies focused on either the dNLR or PNI solely, and there are currently few comprehensive studies of the combined use of preoperative inflammation-based prognostic scores and immunonutritional status for survival prediction in HCC patients. Therefore, we hypothesized that a combined systemic inflammation-based grade, namely the dNLR-PNI, which may represent the co-influence of systemic inflammation, may be a more suitable prognostic marker than these two variables alone. Accordingly, in the present study, we aimed to evaluate the prognostic value of the dNLR-PNI grade in patients with intermediate-to-advanced HCC undergoing TACE.We retrospectively analyzed a population of HCC patients treated with TACE from 2007 to 2013, at our institution. HCC was diagnosed according to the American Association for the Study of Liver Diseases guidelines . The incWritten informed consent was obtained from all patients prior to TACE. The study was approved by the independent ethics committees at the West China Hospital, Sichuan University. The study protocol conformed to the ethical standards of the Helsinki Declaration.3) [The dNLR was constructed as follows: dNLR = neutrophil count to (white cell count-neutrophil count) . The pre3) . ReceiveAll TACE procedures were performed by two operators using the same angiographic system , which has been previously described . Briefly2 test or Fisher’s exact test. OS curves were analyzed using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional hazards model was used for the univariate and multivariate analyses. All factors found to be significant predictors of OS (P < 0.10) in the univariate analysis were entered the multivariate analysis. The multivariate analysis was performed using multivariate Cox proportional hazards regression analysis using a forward selection method. The cut-off values for the dNLR and PNI to predict OS were calculated using ROC curves. Additionally, the area under the receiver operating characteristic curve (AUROC) was calculated to compare the discriminatory performance of each scoring system at 1-, 3-, and 5-year intervals. All statistical analyses were performed using IBM SPSS version 24.0 . A two-tailed P value of < 0.05 was considered significant.All continuous variables are listed as the mean ± standard deviation and were compared using one-way analysis of variance. Categorical variables were compared using the χROC analysis determined optimal cut-off values for dNLR and PNI of 1.7 and 46, respectively, which gave the best sensitivity and specificity for the prognosis of OS, as evaluated by the areas under the curves  were classified as Child–Pugh class A. Hepatitis B infection was the most common etiology of liver cirrhosis . Overall, 72.0% of the patients received more than one TACE treatment (range: 1–8). No significant differences in age, sex, body mass index, alanine transaminase, tumor number, and model for end-stage liver disease score were observed between the groups. The mean aspartate transaminase level, total bilirubin level, prothrombin time, and largest tumor size were significantly higher in group dNLR-PNI 2 than in the other two groups . The proportions of Child-Pugh grade B, vascular invasion, and patients receiving TACE once were also significantly higher in group dNLR-PNI 2. The relationships between the dNLR-PNI value and the clinicopathological characteristics of the patients are shown in Table The median values and ranges of the pre-TACE WBC, neutrophil, lymphocyte, and platelet counts, as well as the dNLR and PNI scores, are shown in Table P < 0.001; Fig. p < 0.001; Fig. P < 0.001; Fig. The median OS for all patients was 12.0 months (95% CI 9.8–14.3); 562 (73.9%) patients died during the follow-up period. The 1-, 3-, and 5-year OS rates were 49.7%, 25.1%, and 12.4%, respectively Fig. . We compP < 0.1) in the univariate analysis were further evaluated to determine their influence on OS by multivariate analysis. Our results demonstrated that elevated total bilirubin , Barcelona Clinic Liver Cancer stage C , and receiving TACE treatment twice  were independent indictors for worse OS of HCC patients. Moreover, dNLR-PNI 1  and dNLR-PNI 2  were also found to be independent prognostic factors for OS  staging system were compared by analyzing the areas under the ROC curves. ROC curves were calculated for the patients’ OS and survival status at the 1-year, 3-year, and 5-year follow-up . Whether these results can be applied to Western populations wherein hepatitis C virus, nonalcoholic steatohepatitis, and other etiologies of liver disease predominate requires further study and discussion.In conclusion, our results revealed that the novel combined inflammation-based immunonutritional score dNLR-PNI is a useful tool in assessing the postoperative survival in intermediate-to-advanced HCC patients after TACE. The dNLR-PNI is simple to calculate from clinical laboratory measures, and is cheap, readily available, and reproducible. Therefore, the dNLR-PNI should be further evaluated as a prognostic marker to predict the outcome of patients with unresectable HCC at the time of diagnosis, as a means to determine the appropriate candidates for TACE treatment.


Obesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10–25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development.Expression data of 60 severely obese individuals was accessible, of which 28 individuals were MHO and 32 were metabolically unhealthy obese (MUO). A whole genome expression profile of four tissues was available: liver, muscle, subcutaneous adipose tissue and visceral adipose tissue. Using insulin-related genes, we used the weighted gene co-expression network analysis (WGCNA) method to build within- and inter-tissue gene networks. We identified genes that were differentially connected between MHO and MUO individuals, which were further investigated by homing in on the modules they were active in. To identify potentially causal genes, we integrated genomic and transcriptomic data using an eQTL mapping approach.IL-6 and IL1B were identified as highly differentially co-expressed genes across tissues between MHO and MUO individuals, showing their potential role in obesity-induced disease development. WGCNA showed that those genes were clustering together within tissues, and further analysis showed different co-expression patterns between MHO and MUO subnetworks. A potential causal role for metabolic differences under similar obesity state was detected for PTPRE, IL-6R and SLC6A5.Both We used a novel integrative approach by integration of co-expression networks across tissues to elucidate genetic factors related to obesity-induced metabolic disease development. The identified genes and their interactions give more insight into the genetic architecture of obesity and the association with co-morbidities. Obesity, characterized by an excessive accumulation of adipose tissue in the body, has major consequences for human health, like type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH). However, it has now been acknowledged that (extremely) obese individuals may also be metabolically and cardiorespiratory fit, so called metabolic healthy obese (MHO) , 2. It iHere, we aim to find genetic and molecular mechanisms important for human obesity-induced disease development by comparing inter-tissue gene co-expression of MHO and metabolically unhealthy obese (MUO) individuals. A study in mice showed important dynamic inter-tissue crosstalk in obesity development, with a key role for inflammatory pathways . Also, tIn this study, 60 severely obese individuals  who underwent elective bariatric surgery were included. All individuals were free from acute or chronic inflammatory or degenerative diseases, and did not consume a high amount of alcohol (>10 g/day) or anti-inflammatory drugs. This study was approved by the Medical Ethical Board of Maastricht University Medical Centre, in line with the guidelines of the 1975 Declaration of Helsinki. Informed consent in writing was obtained from each subject personally. All subjects were deeply phenotyped for a number of metabolic measures, e.g. systemic glucose, cholesterol, and C-reactive protein concentrations.musculus rectus abdominis), subcutaneous adipose tissue , and visceral adipose tissue . RNA was hybridized to Illumina HumanHT12 BeadChips and scanned on the Illumina BeadArray Reader. Raw intensity data were extracted using Illumina’s BeadStudio Gene expression module v3.2. The samples were not pooled. All raw data are publicly available at Gene Expression Omnibus (GSE22070). Raw expression data were normalized by performing a quantile normalization and log2 transformation.During elective bariatric surgery samples were taken from the liver, muscle  and imputed using the GIANT release from the 1000 Genomes project .More information about the study population, expression profiling, and genotyping can be found in previous publications –19.http://geneontology.org), by using the search term “insulin”, resulting in the detection of 92 GO-terms. We then used Biomart [Insulin-related genes were filtered from the expression dataset. First, GO-terms related to insulin were found using AmiGO 2 . This resulted in a correlation between each tissue-pair  for each insulin-related gene in both the MHO and MUO subnetwork. Following this, between each tissue-pair the absolute difference between MHO and MUO subnetworks was calculated for each gene. Then, the sum of tissue-pair differences (inter-tissue co-expression) in both networks was calculated.th gene in the tth tissue and correlated with all other Gi genes in a Tt different tissue and repeated for all genes in G and all tissues in T. Here, T is a vector with the number of tissues and G a vector with the number of genes in a given tissue. The mean and standard deviation of each block showed no significant difference between the within-tissue and inter-tissue blocks, showing no biasing difference in connection strength between within-tissue blocks and inter-tissue blocks. Modules were detected by first calculating the dissimilarity Topological Overlap Measure (TOM), which was used for clustering. Modules were defined as branches of the cluster dendrogram, which were detected using the Dynamic Tree Cut library for R [To gain insight in gene-gene interactions we constructed weighted gene co-expression networks, using the Weighted Gene Co-expression Network Analysis (WGCNA) R-package . The netry for R , with a http://github.com/molgenis/systemsgenetics/tree/master/eqtl-mapping-pipeline [-4), and minor allele frequency (MAF > 0.05). We performed the cis-eQTL analysis, whereby the distance between SNP and probe was set on 1 Mb on either side of the probe. Detected p-values were corrected for multiple-testing by permutation testing (n = 10), and eQTLs were considered to be significant with a FDR < 0.05. The eQTL mapping was performed with the expression data of each tissue.The eQTL mapping was performed using the eQTL-mapping-pipeline (v.1.2.4) developed by the Department of Genetics, University Medical Centre Groningen, The Netherlands, which can be found at pipeline . We usedhttp://humanmine.org), detecting overrepresented GO-terms and KEGG pathways. Visualization of modules was performed in Cytoscape [Genes in detected modules were retained for gene set enrichment analysis (GSEA) based on their Module Membership . GSEA was performed using HumanMine  and underwent bariatric surgery. Deep metabolic phenotyping resulted in an overview of the metabolic state of the individuals, showing that nearly half were MHO (defined as having neither T2D nor NASH). Among the MUO individuals, 18 individuals suffered from T2D , 27 suffered from NASH  and of them, 13 individuals had both T2D and NASH . Descriptive statistics of the metabolic phenotypes showed a significant difference (P < 0.05) between MHO and MUO individuals for glucose, glycated hemoglobin (HbA1c), FFA, and aspartate transaminase (ASAT) . Those met al. [IL1B and IL-6. Both genes showed, most of them significant, stronger inter-tissue co-expression in the MUO subnetwork than in the MHO subnetwork.Dobrin et al.  showed tIL1B) is an important cytokine mainly produced by activated macrophages. IL1B showed a strong correlation between liver and adipose tissues in the MUO subnetwork, with lower correlations among the other tissues and in the MHO subnetwork  with strong correlations between liver and adipose tissues  as these are potentially important in disease development. IL1B and IL-6, expressed in each of the four tissues, did not cluster together across tissues or within the MHO subnetwork. However, they did cluster together in the MUO network, within each tissue. We further investigated those modules and genes, focussing on altered correlations between MHO and MUO subnetworks, to get more insight into the mechanisms involved in disease development. We confirmed that those modules were not age and/or gender dependent, as the module eigengenes of the modules were not significantly correlated with age or gender. While we focused on overall co-expression patterns across tissues in MHO ad MUO individuals, it could be expected that co-expression patterns may differ among patients suffering from either NASH or T2D, however, due to the limited sample size we were not able to home in on them.We constructed two large gene co-expression networks using insulin-related genes in four tissues, resulting in a network for the MHO and for the MUO individuals. Clustering within those networks resultantly can lead to tissue-specific clusters or clusters with genes across tissues. Clustering of the genes in the MHO and MUO network is visualized using a gene dendrogram . We focuIL1B and IL-6 gene, clustered the expression profiles of 29 genes (MM > 0.6) of which 27 are coming from the liver. Two genes in this module (PKM and SLC6A5) are coming from SAT and VAT, respectively. GSEA revealed the NOD-like receptor (NLR) signalling pathway as most significant KEGG pathway (P = 0.002) and GO-terms were associated with signal transduction  and cytokine receptor binding (P = 6.59E-4). Those findings are in concordance with the fact that excessive amounts of adipose tissue result in an increased release of cytokines, e.g IL-6, IL1B, and CCL2, causing inflammation through, for example, the NLR signalling pathway [The Greenyellow module in the MUO network, containing both the  pathway .IL1B and IL-6, with a slight increase in strength between MHO and MUO individuals . In this module, IL1B does not show large alterations in co-expression with other genes between MHO and MUO individuals. However, IL-6 shows and altered correlation with the cytokine suppressor genes SOCS2 (r = 0.01 vs. r = 0.74) and SOCS3 (r = 0.47 vs. r = 0.75), and furthermore, the correlation between SOCS2 and SOCS3 is slightly altered (r = 0.44 vs. r = 0.69). Previous studies have shown that obesity impairs JAK-STAT3 signalling as a result of elevated IL-6 levels, leading to elevated expression of for example SOCS3 in white adipose tissue, liver, and muscle [SOCS3 impairs insulin action and elevated SOCS3 levels are associated with insulin resistance [SOCS3 and IL-6 has been shown before, as the absence of SOCS3 leads to altered effects of IL-6 resulting in a strong inhibiting effect on macrophages and dendritic cells, resembling an inflammatory response [PTPN1 gene, encoding PTP1B, is associated with insulin resistance by negatively regulating insulin signalling [IL-6 in the module between MHO and MUO subnetworks: no correlation was found between PTP1B and IL-6 in the MHO subnetwork, while they were moderately correlated in the MUO subnetwork (r = 0.53).Pearson’s correlation coefficients of genes in the Greenyellow module were visualized in Cytoscape for both sub-networks . Visualid muscle . By bindsistance . The impresponse . Also thgnalling . Due to gnalling . This geSLC6A5 gene, expressed in VAT. SLC6A5 shows generally low correlation coefficients with other genes in the MHO subnetwork, but several strongly correlated genes in the MUO subnetwork. Correlations with IL1B and IL-6 are only moderate in MUO  and low in MHO  subnetworks. The strongest correlations of SLC6A5 within the MUO subnetwork are found with ANXA1 (r = 0.66), CCL2 (r = 0.63), MARCKS (r = 0.61), and SOCS3 (r = 0.61); all of which are not correlated in the MHO subnetwork. SLC6A5 is encoding the neuronal glycine transporter 2 (GlyT2) and its action involves protein kinase C (PKC) pathways [SLC6A5 itself has not been associated with obesity, its regulating properties via PKC pathways might affect the metabolic state of obese individuals. For example, ANXA1  is an idiposity . Likewispathways . We ther in mice .IL1B and IL-6 were filtered out due to the strict threshold on the MM, but were included in comparison of correlation strengths between the MHO and MUO subnetworks. The correlations among them were altered between the MHO and MUO subnetwork . One well-known obesity-genes is Leptin (LEP), encoding leptin, which is also called the “satiety hormone”. In skeletal muscle, it promotes energy dissipation and prevents fatty acid accumulation [LEP shows strong positive and negative correlations with all other Turquoise module-genes (absolute correlation > 0.8) in the MUO subnetwork, while being low with many of the genes in the MHO subnetwork (absolute correlation < 0.4). The largest differential correlation for LEP was found between LEP and PTPRE (0.22 vs. 0.91 in MHO vs. MUO). PTPRE  negatively regulates insulin signaling in skeletal muscle and has been suggested to play a role as negative feedback regulator of leptin signaling via JAK2 [LEP and IL1B (r = -0.15 vs. r = 0.81 in MHO vs. MUO). It has been shown that IL1B is necessary for induction of leptin during inflammation [ADIPOQ), encoding the hormone adiponectin that enhances skeletal muscle insulin sensitivity and has been suggested as a drug target for obesity and T2D [ADIPOQ and IL1B differed to a large extent between MHO and MUO (r = -0.19 vs r = 0.68 in MHO vs. MUO). In adipocytes, but not in skeletal muscle, it has been shown that IL1B reduces adiponectin production, thereby negatively affecting insulin sensitivity [The Turquoise module in the MUO subnetwork  clusteremulation . LEP shoammation . Our dat and T2D . The corsitivity , 29. No PRKAG2  and PIK3R1. The correlation between IL1B and IL-6, and their correlation with cytokine suppressor genes, was similar between MHO and MUO subnetworks in SAT. The two genes that are expressed in VAT, PRKAG2 and PIK3R1, are showing altered co-expression with IL-6 and IL1B. The co-expression of PIK3R1 with IL1B and IL-6 in the MHO subnetwork is very low , but strongly negative in the MUO subnetwork (both -0.67). PIK3R1 encodes part of the phosphatidylinositol 3-kinase (PI3K) enzyme, and PI3K signaling plays an important role in insulin signaling. PIK3R1 is involved in the mediation of insulin sensitivity and the inflammatory response in adipose tissue [PIK3R1 indicates an important role in disease development that has been identified by others as well [PRKAG2 with IL1B and IL-6 is around zero in the MHO, but moderately positive in the MUO subnetwork . PRKAG2 is part of the AMP-activated protein kinase (AMPK) pathway, which is important in energy regulation, e.g. glucose homeostasis and insulin sensitivity [The Black module in the MUO subnetwork  clusteree tissue . The alt as well . The corsitivity . Due to IL-6R). Many of the correlations between IL-6R and other genes were not altered between MHO and MUO subnetworks. However, the correlation with SOCS3 was elevated  and with PIK3R1 (in VAT) was decreased . Surprisingly, the correlations of IL-6 with those genes were unaltered, implicating an important role for the receptor of IL-6, also based on previous discussion of results for the JAK-STAT pathway, in obesity-induced disease development. Several altered phenotypes have been detected in mutations in the IL-6 receptor in mice, e.g. insulin resistance and inflated inflammatory action [In this module we found one eQTL: the IL-6 receptor (y action . Howevery action .STX4) that was coming from both SAT and VAT. Several genes from previously discussed modules were also present in this module. The co-expression of IL1B and IL-6 with SOCS2 and SOCS3 is similar to the co-expression found in SAT (Black module), meaning that their correlation is only altered in the liver. Also the co-expression between IL1B and IL-6 is unaltered in SAT. The co-expression between STX4 in SAT and VAT is stronger in the MUO than in the MHO subnetwork . The co-expression of STX4 in SAT is altered with IL1B, the IL1B receptor antagonist (IL1RN), IL6, and the IL-6 receptor (IL6R). In all four cases, the co-expression is moderate to strongly positive in the MUO subnetwork and low negative co-expressed in the MHO subnetwork. However, the co-expression of STX4 in VAT with the four genes that were expressed in VAT is similar between MHO and MUO subnetworks, suggesting a role in disease development for STX4 only in SAT.The Salmon Module in the MUO subnetwork  clusterePTPRE, expressed in VAT. PTPRE is a negative regulator of insulin signalling in muscle [PTPRE was differentially expressed and methylated before and after bariatric surgery, and that NASH phenotype was negatively correlated with the bariatric reconstruction [PTPRE as eQTL, the PTPRE gene is present in all four modules that were further investigated due to presence of IL1B and IL-6. Homing in on the cross-tissue talk of this gene, the main change is found between the correlation in liver and VAT (0.05 vs 0.55 in MHO vs. MUO). In the Salmon module PTPRE shows altered co-expression with the previously discussed ISL1 gene (0.07 vs -0.60 in MHO vs MUO), encoding the insulin gene enhancer protein ISL-1. Many of the correlations of ISL1 with other genes in this module are altered, with strong negative correlations in the MUO subnetwork. Previously, it has been shown that ISL1 is expressed in VAT and negatively correlated with BMI and abdominal fat [PTPRE in liver with e.g. SLC6A5 (VAT), SLC6A13 (liver) and PKM (SAT). It is remarkable that the module consists of mostly genes co-expressed in the liver, but that PTRPE shows altered co-expression with the two genes that are coming from SAT and VAT, suggesting an important function for PTPRE as a link between tissues in disease development resulting from obesity. To date, no studies have linked PTPRE with any of those genes.In this module we found one eQTL: n muscle . In a sttruction . Besidesinal fat . They alIL-6 and IL1B as key genes for inter-tissue gene co-expression differences related to metabolic state. By investigating the modules in which IL-6 and IL1B were co-expressed, we detected many altered co-expressed genes and pathways that might be important in obesity-induced inflammation and comorbidity development. Even though IL-6 and IL1B mRNA levels were not altered between MHO and MUO individuals in our study, their co-expression with other genes indicates a potentially important role in obesity-induced development of metabolic disturbances. The chosen approach gave us insight into co-expression between genes in a network setting, but could not give information about directions in the network. However, an eQTL mapping approach was chosen to detect genes that affect mRNA levels and thereby affecting health status. This led to the identification of several genes  which might have an important role in insulin-related pathways of obese individuals. Functional validation of those genes is needed to identify their potential role in the development of obesity-induced comorbidities.In summary, we have shown the integration of gene co-expression networks across tissues in MHO and MUO individuals to identify genes and pathways related to obesity-induced disease development. The results provide important insights into genomics of adipose tissue expandability, lipotoxicity, and eventual comorbidities such as T2D and NASH. In a co-expression network setting, we detected S1 FigClustering is based on the dissimilarity Topological Overlap Measure (TOM) within the A) metabolically healthy obese (MHO) and B) metabolically unhealthy obese (MUO) network. Modules are detected using the Dynamic Tree Cut algorithm and presented by the color-coded bar under the dendrogram.(PNG)Click here for additional data file.


The risk of tuberculosis (TB) is greater for individuals with human immunodeficiency virus (HIV) who are on combined antiretroviral therapy (c-ART) than for the normal population. Therefore, the detection and treatment of latent tuberculosis infections is recommended for all HIV-positive persons with positive tuberculin skin tests (TSTs).This retrospective cohort study included all HIV-positive individuals with CD4 lymphocyte counts greater than 200 cells/μL and negative TST results, who were taking antiretroviral drugs and had been referred to Imam Khomeini Teaching Hospital Consultation Centre for Clients with Risky Behaviors in Tehran, Iran, from 2008 to 2013. TST conversion to positivity is defined as an induration increase of at least 5 mm compared with a previously negative TST result within a 1-year period. Conversion rates are expressed in person-years of observation.A total of 113 patients were included in our study. At 1 year, 9 of the 113 TST-negative patients taking c-ART became TST-positive . The TST conversion incidence rate was 10.09/100 person-years. TST conversion was only found to be associated with sex .Our results suggest that TSTs should be administered to all HIV-positive patients before beginning isoniazid preventive therapy in Iran. Tuberculosis (TB) is a leading cause of death in developing countries, especially among HIV-positive people. HIV-infected individuals are at a higher risk for reactivation of latent TB infections or new TB infections than are healthy people; furthermore, the clinical presentation of TB in HIV-infected persons is more complicated ,2. In a The lifetime risk of TB reactivation is 20% among HIV-infected people, which is defined by a 10-mm or greater induration in a tuberculin skin test (TST). A TST reaction, using purified protein derivative (PPD) in the Mantoux technique, is useful method for latent tuberculosis infection (LTBI) screening . HoweverThis study aimed to evaluate the TST reaction and its yearly conversion in HIV-infected persons who had CD4 counts ≥200 cells/μL and were TST-negative at the beginning of combined anti-retroviral therapy (c-ART) in a Consultation Centre for Clients with Risky Behaviors in Imam Khomeini Teaching Hospital.This retrospective cohort study included all HIV-infected individuals with CD4 lymphocyte counts greater than 200/μL and negative TST results who were taking antiretroviral drugs and presented to our center between 2008 and 2013. History-taking and physical examination were performed by experienced physicians. Demographic data including age, sex, the possible route of infection, CD4-positive lymphocyte counts, TST results, and chest radiography findings  were recorded. We excluded individuals with diabetes mellitus, end-stage renal disease, or chronic liver disease; individuals who were taking immunosuppressive drugs; and patients younger than 13 years of age.In our clinic, TSTs were performed for all new patients with HIV infection. If a TST result was negative, we repeated the test in 1 year. All results were recorded. We performed the TSTs using the Mantoux technique, with 0.1 mL of PPD  administered intradermally. The dermal reaction was interpreted by an expert nurse or physician after 48–72 hours. A positive TST result was defined as an induration of ≥5 mm. A positive TST conversion was defined by a ≥5-mm increase in induration compared with a previously negative TST result in a period of 1 year.p value of <0.05 was considered to be significant. Conversion rates are expressed in person-years of observation.Statistical analysis was performed using SPSS 18 statistical software . Results are expressed as means ± standard error (SE). The chi-square test and t-test were used for analytical comparison. A This study was approved by both the Deputy Research of Iran and Tehran Universities of Medical Sciences (NO. 1399).From 2008 to 2011, we evaluated 550 individuals with HIV infection. A total of 437 individuals were excluded: 194 patients had CD4-positive lymphocyte counts lower than 200 cells/μL, 52 patients were not receiving c-ART, 29 patients were younger than 13 years of age, 25 patients did not have complete records, 16 patients received c-ART in other centers, 23 patients had active tuberculosis, and 98 patients had positive TSTs at baseline. In all, 113 patients were included in our study.The mean age of the patients was 37.82 ± 9.11 years. Demographic data are shown in In our study population, there was no association between CD4 cell count increment, baseline CD4 cell count, and TST conversion. Of the demographic characteristics, only female sex was found to be associated with TST conversion. Radiologic findings, history of IPT, and history of TB disease/treatment were not associated with TST conversion. CD4 cell count and its increment after 12 months were significantly different between females and males .All of our patients had a history of Bacille Calmette-Guerin vaccination. No patients developed active TB during the 1-year follow-up period.In this study over a period of 12 months after c-ART initiation, 9 of 113 (8%) TST-negative patients experienced TST conversion—an incidence rate of 10.09/100 person-years. We found a lower rate of TST conversion than other studies ,7. Thesep = 0.99). However, none of the patients with a positive history of IPT and TB treatment were in the converter group, so this association should be further investigated in a large-scale study. The direct effects of IPT for preventing disease after household contact with a TB-infected individual have been reported previously , which is in line with a study from Uganda . In anotp < 0.0001)  . These r 0.0001) . One stu 0.0001) .p < 0.001). More frequent side effects were also reported for all classes of antiretrovirals in women (In line with a previous study , the womin women . Other sin women , 21.Oni et al. reported an 8.5% prevalence rate for asymptomatic TB disease among HIV-infected persons. The authors showed that 61% of patients with subclinical TB had a CD4 count of >200 cells/μL; however, a low CD4 count appeared to be predictive of subclinical TB . The TSTSome studies reported that IPT caused a greater reduction in the risk of active TB for TST-positive HIV-infected adults than in TST-negative adults ,23. In o


The implicit self-recognition process may take place already in the pre-attentive stages of perception. After a silent stimulus has captured attention, it is passed on to the attentive stage where it can affect decision making and responding. Numerous studies show that the presence of self-referential information affects almost every cognitive level. These effects may share a common and fundamental basis in an attentional mechanism, conceptualized as attentional bias: the exaggerated deployment of attentional resources to a salient stimulus. A gold standard in attentional bias research is the dot-probe paradigm. In this task, a prominent stimulus (cue) and a neutral stimulus are presented in different spatial locations, followed by the presentation of a target. In the current study we aimed at investigating whether the self-face captures, holds and biases attention when presented as a task-irrelevant stimulus. In two dot-probe experiments coupled with the event-related potential (ERP) technique we analyzed the following relevant ERPs components: N2pc and SPCN which reflect attentional shifts and the maintenance of attention, respectively. An inter-stimulus interval separating face-cues and probes (800 ms) was introduced only in the first experiment. In line with our predictions, in Experiment 1 the self-face elicited the N2pc and the SPCN component. In Experiment 2 in addition to N2pc, an attentional bias was observed. Our results indicate that unintentional self-face processing disables the top-down control setting to filter out distractors, thus leading to the engagement of attentional resources and visual short-term memory. Although being yourself is a profound and undeniable belief, it is not obvious from a functional perspective. The unconscious machinery that is the cornerstone of the self works perpetually in order to recognize as well as consolidate different and temporally separated pieces of self-related information into one coherent whole McAdams, . WithoutThe ability to cognitively identify oneself as an object in the environment, which is self-recognition . Both of them were intended to reveal attention-grabbing properties of self-face as operationalized by the emergence of a lateralized event-related potentials (ERPs) component N2-posterior-contralateral, N2pc  participated in the study. All participants had normal or corrected-to-normal vision and reported no history of mental or neurological disorders. Twenty of these subjects were right-handed, as assessed by the Edinburgh Handedness Inventory  between the ages of 24 and 35 , participants were seated in a comfortable chair in a dimly lit and sound-attenuated room. During the task, an adjustable chin rest maintained head position and a constant viewing distance of 72 cm. The dot-probe task was presented on a Flex Scan EV-2450  computer screen through an Intel Core i3 computer running Presentation® software . The screen was specially calibrated for correction to black in order to not exhaust eyes with intense background illumination. EEG signal was amplified using QuickAmp and digitized using BrainVision Recorder® software .The stimuli consisted of bilaterally presented pairs of gray-scaled face photographs. Depending on the condition, stimuli pairs contained either a self-face and an other-face or two other-faces. Twenty-six  other-face photographs were taken from the A series of the Karolinska Directed Emotional Faces database  which remained onscreen for the duration of the trial. After 1,000 ms, a pair of faces was presented bilaterally. In order to minimalize the occurrence of readiness potentials, the face-cues were presented for either 150 or 600 ms  was continuously recorded with 64 Ag-AgCl electrically shielded electrodes mounted on an elastic cap  and positioned according to the extended 10–20 system. For ocular artifact scoring, vertical and horizontal electrooculograms (EOGs) were recorded from bipolar electrodes placed at the supra- and suborbit of the right eye and at external canthi of eyes. EEG electrode impedances were kept below 10 kΩ. The data were amplified using a 128-channel amplifier  and digitized at a 500 Hz sampling rate. The EEG signal was recorded against an average of all channels calculated by the amplifier hardware. Offline, the 62 channels were re-referenced to the algebraic average of the left and right earlobes, notch filtered at 50 Hz and digitally band-pass filtered from 1 to 30 Hz using a zero-phase Butterworth filter (12 dB/oct).M = 138, SD = 14), 150 ms cue presentation time . The mean number of segments in Experiment 2 which passed the artifact rejection procedure was as follows: 150 ms cue presentation time , 50 ms cue presentation time . The number of epochs used to compute ERPs did not differ significantly between conditions .Occipital-temporal channels PO8 and PO7 were chosen for the ERPs analysis. These electrodes are frequently reported by many authors as disclosing maximal N2pc amplitudes  = 27.738, p < 0.000, ηp2 = 0.620, showing that the subjects were faster in response when the self-face was presented for 600 ms (M = 370.5 ms) than for 150 ms (M = 383.4 ms). Other effects and interactions were non-significant.All trials with RTs shorter than 100 ms and longer than 1,000 ms were excluded from analysis. Mean RTs for correct trials were computed for each participant for each condition  = 17.618, p < 0.001, ηp2 = 0.509. This indicates a clear N2pc for both cue presentation times quantified as more negative mean amplitudes of the contralateral (M = 1.455 μV) than the ipsilateral (M = 2.242 μV) waveform. The main effect of “cue presentation time” also reached significance, F = 16.835, p < 0.001, ηp2 = 0.498, showing more negative amplitudes for 150 ms than 600 ms of self-face presentation. The interaction between these two factors was non-significant.A two  × two (cue presentation time: 150 ms vs. 600 ms) repeated measures ANOVA yielded a significant main effect of laterality, F = 9.424, p < 0.05, ηp2 = 0.357, indicating that an SPCN was only present when the cue was displayed for 600 ms. The factor of “cue presentation time” also obtained a significant main effect, F = 5.320, p < 0.05, ηp2 = 0.238, showing more negative amplitudes for 600 ms than 150 ms of cue presentation time.The repeated measures ANOVA performed on “laterality” and “cue presentation time” yielded a significant interaction between these two factors, F = 3.996, p < 0.05, ηp2 = 0.190, indicated a significant difference in reaction times. Post-hoc tests revealed that overall participants were faster in response when the target appeared in the visual field previously occupied by the self-face (M = 368.9 ms) than in the incongruent condition (M = 375.6 ms), pb < 0.05. The main effect of “cue presentation time” also reached significance, F = 18.915, p < 0.001, Based on the mean percentage of trials contaminated with ocular artifacts per participant, the same three participants as in the ERP analysis were excluded from the sample. Descriptive statistics regarding every experimental condition are presented in Table F = 28.552, p < 0.001, ηp2 = 0.627, indicating that overall the mean amplitudes of the contralateral waveform were more negative (M = 0.423 μV), than the mean amplitudes of the ipsilateral waveform (M = 1.397 μV). The main effect of “cue presentation time” also reached significance, F = 7.916, p < 0.05, In order to assess the presence of the N2pc component a two  × two (cue presentation time: 150 ms vs. 50 ms) repeated measures analysis of variance was performed. It yielded a significant main effect of laterality, The aim of the current study was to examine whether the self-face captures automatic attention and as a consequence produces an attentional bias. Additionally, we assessed the attentional hold effects of this stimulus. The time course of the attentional effects was investigated using the ERP technique, which allowed us to trace the neural basis and the time-course of cognitive processes that occur very fast. Our analysis was focused on two ERPs components, N2pc and SPCN which reflect attentional shift and the engagement of visual short-term memory, respectively. On the behavioral level, attentional bias was evidenced by comparing RTs to targets preceded by self-face in comparison to RTs to targets preceded by other-faces. In general, the findings of this study supported all our predictions.In line with our predictions, the self-face elicited a clear N2pc component in both dot-probe tasks: with and without a time delay between onsets of the cue (involving bottom-up processes) and target (involving top-down processes). The emergence of N2pc reflects the self-face's attention-grabbing properties on a neural level. Previous ERP studies on self-face recognition suggested such enhanced attentional processing; however, without specifying the stage of processing in which this effect occurs  self-face cue presentations, indicating an attentional hold effect. This component has been typically observed when the task required encoding the peripheral stimulus and is associated with visual short-term memory  as revealed by our and Grimshaw et al.'s experiments . As a coAt the end, we would like to comment on future directions in the field of the self-research. The neural basis of self-face recognition has been extensively investigated, resulting in various neuroanatomical network models (Kircher et al., MW and AN developed the study concept. All authors contributed to the study design. Testing and data collection were performed by all authors. MW and MN performed the data analysis and interpretation under the supervision of AN. MW and AN wrote the manuscript. All authors approved the final version of the manuscript for submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this study, the development and progression of infection and inflammation were monitored on rats by using 18F-FDG via PET/CT.Detection/localization of infection and inflammation is important for the initiation of correct treatment as well as its maintenance. Nuclear medicine imaging methods play an important role in determining infection and inflammation. S. aureus, respectively. For evaluation of the formation and progression of the abscess, 18F-FDG was injected into the rats and they were imaged by PET/CT at intervals of twenty-four hours for five days. Maximum standard uptake value (SUVmax) of 18F-FDG was calculated.Sterile and infected abscesses were formed on rats using turpentine and max of the S. aureus abscess was 3.9±0.9 while in the sterile abscess SUVmax in the first day was 2.2±0.8. 18F-FDG uptake decreased day by day and it reached the background level on the fourth and fifth days. There were statistically significant differences between S. aureus and sterile abscess, and between sterile abscess and background activity in terms of SUVmax values during the first three days (p<0.05). On the fourth and fifth days, there was no statistically significant difference between S. aureus and sterile abscess, and between sterile abscess and background activity (p>0.05).The highest activity involvement was seen on the first day of abscess formation. On the first day, SUVmax value for 18F-FDG can be useful in the early differentiation of sterile and infected abscess. In addition, 18F-FDG-PET imaging has the advantage of local availability of equipment and labeled agents leading rapid diagnosis of differentiation of infection and inflammation.The results demonstrated that the SUV They were male White Wistar Rats, clinically healthy animals of 150-220 gr body weight.In this study, sterile abscess was induced by using turpentine and infected abscess was induced by using S. aureus strain (ATCC 25923) was grown in 5-10% sheep blood agar  after incubating overnight at 37°C.S. aureus colonies was suspended in Mueller Hinton broth (mhb) containing tube to obtain l07 colony-forming units (CFU)/mL.One loop of the S. aureus 0.5 mL 107 CFU/mL was inoculated in the right arm of the rats subcutaneously. For sterile abscess formation on rats (n=7) 0.2-0.4 mL turpentine (Sigma-Aldrich) was injected into the right arm of the rats subcutaneously. In the control group (n=6), 0.5 mL 0.9% NaCl was injected into the right arm of the rats subcutaneously. Following each imaging, an abscess of a rat was removed in the another S. aureus group and living bacterial organisms were counted in the excised tissue.The animals were anesthetized by intraperitoneal administration of xylazine, 5 mg/kg and ketamin, 35 mg/kg. For infected abscess formation on rats (n=14), S. aureus and turpentine. 18F-FDG (37 MBq) was injected intravenously via the tail vein. Prior to 18F-FDG injection, rats fasted for 4 hours and were well hydrated. Imaging was performed using PET/CT (PHILIPS Gemini TF), beginning one hour after injection of 18F-FDG on the first day for five days with an interval of twenty-four hours. 18F-FDG rat imaging was done with two-minute bed positions. On the first day, imaging was performed at the first and second hours after injection of 18F-FDG to obtain optimum imaging time. Non-diagnostic CT images were obtained .A preliminary study was performed to optimize imaging time depending on abscess formation. First day image was acquired 24 hours after inoculation of max was obtained from the images for evaluation of glucose metabolism of infection and inflammation detected by 18F-FDG-PET/CT.PET/CT images were visually and semi-quantitatively assessed. For semi-quantitative analysis of the PET images, a region of interest (ROI) was drawn around the abscess area on the right arm. In the control group, a ROI was drawn around a similar area as the background on the right arm. SUVmax of 18F-FDG uptake were calculated on abscess sites by using the formula:The SUVSUV=Tissue concentration (Bq/g)/[injected dose (Bq)/body weight (g)]S. aureus or turpentine, swelling was apparent in the abscess site. A soft tissue infection developed on the right arm within twenty-four hours after bacterial inoculation. Swelling and redness of the abscess area were apparent in all rats. Abscess sites were visualized by 18F-FDG-PET/CT. A higher abscess/background ratio was detected at the first hour compared to the second hour after injection of 18F-FDG. Imaging time was chosen as the first post injection hour for the following days.Twenty-four hours after inoculation of max for S. aureus was 3.9±0.9 on the first day, while it was 2.2±0.8 for sterile abscess and 1.2±0.5 for control group rats. The first day SUVmax on the second hour following 18F-FDG injection was 2.8±0.6 for infected abscess, 1.9±0.9 for sterile abscess, and 1.2±0.09 for control group. During the following two days, although activity involvement decreased at S. aureus it was still higher than involvement in turpentine abscess. There were statistically significant differences between S. aureus and sterile abscess, and between sterile abscess and control group as SUVmax for the first three days (p<0.05). On the fourth and fifth days, there was no statistically significant difference between S. aureus and sterile abscess, and between sterile abscess and control group (p>0.05).The initial SUVmax of infected abscess was higher than that of sterile abscess in all images during the first three days. CFUs per milliliters (CFU/mL) in excised abscess tissue was 104 CFU/mL, 103 CFU/mL, 102 CFU/mL in the first, second and third days, respectively. There was no living organism at the fourth and fifth days. A correlation was detected between 18F-FDG activity and number of living microorganisms in excised abscess tissue.It was observed that SUV18F-FDG images of sterile and infected abscess in rats.max for sterile abscess, infected abscess, and control rats as well as the quantity of living organisms. In vitro labeled leukocyte imaging is the gold standard for imaging most infection. However, preparation of this radiopharmaceutical is laborious, time consuming and requires handling of potentially contaminated blood  resolution of the images would have been higher than the presented images.In our study, the highest 18F-FDG as a glucose analog can be used for diagnosis of infection and inflammation. Sterile and infected abscess differentiation can be evaluated by imaging with 18F-FDG-PET at early phase. The value of SUVmax explores correlation between sterile abscess and infected abscess. 18F-FDG-PET is also a useful technique to understand the extent of the infection and inflammation process. In addition to PET imaging method with 18F-FDG has the possibility of rapid diagnosis and easier with the advantage of local availability.Inflammatory and infected tissues utilize glucose as energy source for chemotaxis and phagocytosis. Therefore, the accumulation of


Enterobacteriaceae in Africa remain rare and assess mostly blaOXA-48–producing isolates from Mediterranean countries and South Africa. We identified blaNDM-7–producing Enterobacteriaceae in Gabon in 2016. The isolates contained blaNDM-7 IncX3 plasmids that were unusual and similar to the one described in a colistin-resistant Klebsiella pneumoniae SZ04 isolate from China.Reports of carbapenemase-producing  Enterobacteriaceae (CPE). A new type of β-lactamase, blaNDM, was reported from a patient in Sweden in 2007 . The swabs were placed in 0.5 mL sterile water; 0.1 mL of the resulting suspension was streaked onto a selective agar plate provided for the identification of bacteria resistant to third-generation cephalosporins . The plates were incubated for 48 h at 35°C. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology  to confirm each isolate thought to be http://www.eucast.org/). Isolates resistant to second- and third-generation cephalosporins were investigated for MIC of ertapenem using Etest  and for carbapenemase production by the CarbaNP test (bioMérieux). For molecular characterization, we performed Sanger sequencing of PCR amplicons of the gene. Purified genomic DNA of the blaNDM-producing isolates was subjected to whole-genome sequencing on a HiSeq system . Reads were filtered for quality with fastq-mcf (Ea-utils: http://code.google.com/p/ea-utils). We used Edena version 2 for genome assembly  and remained susceptible to tigecycline. We enrolled a total of 138 patients  in the study. The population had poor health status . Recent hospitalization and antimicrobial drug therapy were reported for 32.5% and 15.9% of patients, respectively. CPE carriage was found in 7 (5.1%) patients and was associated with neonates (p<0.001). The CPE isolates harbored multiple antimicrobial resistance genes (but no blaOXA-48 and 4 a blaNDM-7 determinant (LC154935.1)  to an IncX3 plasmid in a mcr-1 blaNDM-5–producing Klebsiella pneumoniae strain isolated from a patient from China (blaNDM-7 CPE was unexplained.Three isolates harbored 54935.1) . blaNDM-K. pneumoniae, including sequence type 307  of sequence type 307. This result suggests an uncontrolled spread in the hospital intensive care unit.Because of the social and economic relationships between China and Gabon, the travels of asymptomatic CPE carriers from China to Gabon can be expected to have facilitated the spread of CPE in Gabon. Several multidrug-resistant clones of blaNDM-7 in Africa highlights the international dissemination of carbapenemase determinants and the combination of 2 aggravating factors, resulting in an alarming situation: the identification of blaNDM-7 within a transposon element on a conjugative plasmid with a potentially very high level of transmissibility, and the implication of the presence of K. pneumoniae, a pathogen with a high potential to persist and disperse in the hospital environment. Urgent measures are required, including the rational use of antimicrobial drugs, public education on the importance of hygiene, and diligent surveillance to control the spread of these multidrug-resistant organisms in the hospital setting.This description of